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Signaling Neuronal Migration

During the development of the central nervous system, cell motility plays a key role in the proper positioning of neurons. Although a wide range of growth factors has been shown to control motility in cells, those involved in neuronal migration have not been fully characterized. However, recent studies have suggested that hepatocyte growth factor (HGF) and the HGF receptor tyrosine kinase Met play a role in neuron migration.

Model of signaling requirement for cortical neuron migration induced by HGF/Met.

In this Paper of the Week, Joseph Segarra and colleagues lend support to this observation by elucidating the intracellular pathways controlling neuronal migration triggered by Met. Using cells with altered Met docking sites as well as pharmacological inhibitors of downstream signals activated by the receptor, the researchers show that the Ras/ERKs and phosphatidylinositol 3-kinase (PI3K) pathways are both required for cortical neuron migration. By dissecting the downstream signals necessary for migration, Segarra et al. are also able to show that the PI3K effectors Rac1/p38 and Akt are required, whereas the c-Jun N-terminal kinase (JNK) and mTOR/p70^s6k pathways are dispensable.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 4771-4778

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